Mast cells play a pivotal role in the pathogenesis of asthma and other allergic diseases. Such conditions are generally initiated by antigen- dependent aggregation of the high affinity IgE receptors (Fc-epsilon- RI) expressed on the cell surface and subsequent release of pro- inflammatory mediators (e.g. histamine, prostanoids, proteases and cytokines). Recent data from LAD has demonstrated that interferon gamma up-regulates the high affinity receptor for IgG (FcgammaRI) in cultured human mast cells and the aggregation of these receptors also leads to mast cell mediator release. The aim of this study is to delineate the signaling pathways linking the Fc-epsilon-RI and Fc-gamma-RI receptors to the release of inflammatory mediators from human mast cells.The current model for the signaling pathway linking the Fc-epsilon-RI to mast cell activation has largely been based on studies conducted in RBL 2H3 cells. The primary reason for this has been an inability to obtain sufficient human mast cells for these studies. However, RBL 2H3 cells are a transformed rodent cell line, which may not be truly reflective of the mature human mast cells, which are terminally differentiated and non-proliferative. The signaling pathways linking the Fc-gamma-RI receptor to mast cell activation has yet to be delineated. Recently, a technique has been developed in the LAD, which allows us to grow human mast cells from a CD34 positive, pluripotent cell population in primary culture with sufficient number and purity to study defined signaling events. Thus, it will now be possible to delineate the importance of specific signaling pathways involved in Fc-epsilon-RI- and Fc-gamma-RI- dependent inflammatory mediator release from human mast cells. - Fc- epsilon-RI, Fc-gamma-RI, Fc-gamma-RII, Fc-gamma-RIII, signaling, cytokines, allergy, asthma, mast cells, basophils